Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep 21;9(47):8871-8875.
doi: 10.1039/c8sc03754j. eCollection 2018 Dec 21.

Copper-mediated 1,2-bis(trifluoromethylation) of arynes

Xinkan Yang  1 , Gavin Chit Tsui  1
Affiliations

Copper-mediated 1,2-bis(trifluoromethylation) of arynes

Xinkan Yang et al. Chem Sci. .

Abstract

We herein describe an unprecedented 1,2-bis(trifluoromethylation) of arynes with [CuCF3] in the presence of an oxidant DDQ. The method allows the rapid construction of a new class of 1,2-bis(trifluoromethyl)arenes in one-step from aryne precursors under mild conditions. Its synthetic utility has been demonstrated in the preparation of bis(trifluoromethylated) molecules with potential pharmaceutical and materials science applications. Mechanistic studies indicated the presence of an o-trifluoromethyl aryl radical intermediate via CF3 group transfer from [CuCF3] to the aryne.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1. Transition metal-catalyzed/-mediated 1,2-difunctionalization of arynes and applications in trifluoromethylation reactions.
Scheme 2
Scheme 2. Scope of 1,2-bis(trifluoromethyl)arenes 2. aGeneral conditions: 1 (0.4 mmol), DDQ (0.8 mmol), [CuCF3] (1.6 mmol in 4.0 mL DMF), DMSO (8.0 mL), under argon. Isolated yields. bDMF : DMSO = 4.0 : 4.0 mL. cDMF : DMSO = 4.0 : 12.0 mL. dYield determined by 19F NMR analysis using benzotrifluoride as the internal standard.
Scheme 3
Scheme 3. 1,2-Bis(trifluoromethylation) of an estrone derivative.
Scheme 4
Scheme 4. Further transformations of 1,2-bis(trifluoromethyl)arenes 2.
Scheme 5
Scheme 5. Mechanistic studies.
Scheme 6
Scheme 6. Proposed mechanism.
See this image and copyright information in PMC

References

    1. For reviews on aryne chemistry, see:

    2. Dhokale R. A., Mhaske S. B. Synthesis. 2018;50:1.
    3. Feng M., Jiang X. Synthesis. 2017;49:4414.
    4. Garcia- López J.-A., Greaney M. F. Chem. Soc. Rev. 2016;45:6766. - PubMed
    5. Karmakar R., Lee D. Chem. Soc. Rev. 2016;45:4459. - PubMed
    6. Goetz A. E., Shah T. K., Garg N. K. Chem. Commun. 2015;51:34. - PubMed
    7. Yoshida S., Hosoya T. Chem. Lett. 2015;44:1450.
    8. Wu C., Shi F. Asian J. Org. Chem. 2013;2:116.
    9. Dubrovskiy A. V., Markina N. A., Larock R. C. Org. Biomol. Chem. 2013;11:191. - PubMed
    10. Tadross P. M., Stoltz B. M. Chem. Rev. 2012;112:3550. - PubMed
    11. Gampe C. M., Carreira E. M. Angew. Chem., Int. Ed. 2012;51:3766. - PubMed
    12. Wenk H. H., Winkler M., Sander W. Angew. Chem., Int. Ed. 2003;42:502. - PubMed

    1. For reviews on the synthesis and applications of trifluoromethylated arenes, see:

    2. Alonso C., Martínez de Marigorta E., Rubiales G., Palacios F. Chem. Rev. 2015;115:1847. - PubMed
    3. Liu T., Shen Q. Eur. J. Org. Chem. 2012;2012:6679.
    4. Tomashenko O. A., Grushin V. V. Chem. Rev. 2011;111:4475. - PubMed
    1. Zeng Y., Zhang L., Zhao Y., Ni C., Zhao J., Hu J. J. Am. Chem. Soc. 2013;135:2955. - PubMed
    2. Zeng Y., Hu J. Chem.–Eur. J. 2014;20:6866. - PubMed
    3. Zeng Y., Hu J. Synthesis. 2016;48:2137.
    1. Yang X., Tsui G. C. Org. Lett. 2018;20:1179. - PubMed
    1. Yoshida H., Ikadai J., Shudo M., Ohshita J., Kunai A. J. Am. Chem. Soc. 2003;125:6638. - PubMed
    2. Yoshida H., Tanino K., Ohshita J., Kunai A. Angew. Chem., Int. Ed. 2004;43:5052. - PubMed
    3. Yoshida H., Kawashima S., Takemoto Y., Okada K., Ohshita J., Takaki K. Angew. Chem., Int. Ed. 2012;51:235. - PubMed
    4. Pareek M., Fallon T., Oestreich M. Org. Lett. 2015;17:2082. - PubMed